Genetic Testing Reduces Chemotherapy Risks for Gastrointestinal Cancer Patients

For patients with gastrointestinal cancers such as colorectal and pancreatic cancer, standard chemotherapy doses can trigger severe and sometimes life-threatening side effects in those carrying specific genetic variants. These differences affect how the body processes key drugs, yet current protocols rarely account for them. Now, a new study shows that pre-treatment genetic testing can guide safer, tailored dosing and cut harmful reactions significantly.

Researchers at the Perelman School of Medicine at the University of Pennsylvania (Philadelphia, PA, USA) evaluated a precision medicine approach that screens for two gene variants—DPYD and UGT1A1—before starting chemotherapy. The DPYD gene helps the liver break down fluoropyrimidines, while UGT1A1 affects irinotecan metabolism. Variants can slow drug clearance, causing dangerous toxicity. Identifying these risks allows doctors to reduce doses without compromising cancer treatment effectiveness.

Image: The study showed tailored doses cut severe side effects (Photo courtesy of 123RF)

The study enrolled 517 GI cancer patients across three Penn Medicine sites who were set to receive fluoropyrimidine or irinotecan. Of these, 288 underwent blood tests to detect the gene variants. Results were returned in about a week, enabling clinicians to adjust initial dosing for high-risk patients. The approach was compared with variant carriers from a biobank group who received standard doses without genetic screening.

The findings, published in JCO Precision Oncology, showed that among 16 variant carriers in the tested group given reduced doses, 38% experienced severe adverse events. In contrast, 65% of 17 variant carriers in the non-tested group had such side effects. The tested group also had fewer treatment changes (38% vs. 76%) and fewer discontinuations (31% vs. 47%), underscoring the safety benefits of personalized dosing.

With nearly 290,000 new GI cancer diagnoses annually in the U.S., the results highlight a scalable way to reduce complications and improve patient outcomes. The researchers suggest broader adoption could prevent up to 1,300 deaths each year linked to chemotherapy toxicity.

"For too long, the U.S. lagged behind Europe in adopting genetic testing for chemotherapy dosing, but our study shows it’s not only feasible but also critical for patient safety," said Sony Tuteja, lead author of the study.

Related Links:
Penn Medicine